Medical drug formulation and delivery system and reverse osmosis purification device

ABSTRACT

A reverse osmosis device for purifying water from a source comprising a housing having an inlet for passage of water from the source, a first outlet for passage of purified water from the housing and a second outlet for passage of waste water remaining after purification. A first reverse osmosis multilayer assembly is disposed within the housing in fluid communication with the inlet for purification of at least a first portion of the water from the source. Water treatment chemicals can be positioned in a core about which the first reserve osmosis multilayer assembly is wound. The treatment chemicals are in fluid communication with the first reverse osmosis multilayer assembly to receive the first purified portion of water and for removal of at least chemical contaminants therefrom. A second reverse osmosis multilayer assembly is also wound on the core and is in fluid communication with the water treatment chemicals to receive the chemically purified water for purification of at least a second portion thereof. The second reserve osmosis multilayer assembly is in fluid communication with the first outlet so as to permit passage of the second portion of purified water therethrough.

This is a division of application Ser. No. 07/570,660, filed Aug. 20,1990, now abandoned.

The present invention relates to a device for purifying fluids and inparticular to a reverse osmosis device for use, for example, insterilizing and purifying fluids serially through at least two reverseosmosis stages, for use in a system for medical drug formulation anddelivery and for other end use applications.

BACKGROUND OF THE INVENTION

The purification or separation of fluids using synthetic membranes canbe advantageously used in many industrial, medical and homeapplications. Typical membrane separation processes include gas andvapor diffusion, dialysis, ultrafiltration and reverse osmosis.

Synthetic polymeric membranes can be applied to gaseous systems toseparate gaseous solutions into their components. The membrane used inthe gaseous systems must be permeable and selective, possess chemicaland physical stability and be free of structural irregularities such aspinholes. The containing vessel should be capable of supporting thesemembranes under large pressure differentials; have a large membranesurface area per unit volume; cause a minimum pressure drop in the gasstreams; and be inexpensive, i.e., be constructed of low-cost materialswhich are easy to fabricate and assemble. An example of such gasseparation using synthetic membranes is the recovery of helium fromnatural gas and of oxygen from air. Such membrane separation processes,however, are often not competitive to known cryogenic processes becauseof the high power requirements for membrane separation.

Synthetic polymeric membranes have been applied to dialysis wherein somesolutes selectively permeate through the membrane based on theconcentration gradient across the membrane. While the dialysis processis not particularly rapid, it has been industrially utilized, forexample, in the recovery of caustic from rayon and the recovery of spentacid from metallurgical liquors.

Ultrafiltration typically involves the separation of large soluteparticles from the solvent of the solution by forcing the solvent topass through a membrane while the particles are retained to a greater orlesser extent. Often the separation involves a physical sieving of theparticles which are retained on top of the membrane filter. Formembranes of low pore radius, however, the process of ultrafiltrationbegins to overlap the process of reverse osmosis wherein the physicalsieving phenomena is increasingly replaced with the adsorption andsolubility of the solute within the membrane. The retained solutesconsequently can have significant osmotic pressures which must beovercome by higher fluid pressures.

Hemodialysis is an example of a dialysis process which is assisted byultrafiltration. A hemodialyzer is a membrane-containing device which isable to remove certain waste products such as urea, creatinine and uricacid from the blood. The patient's blood is introduced into thehemodialyzer preferably under the patient's own perfusion pressure andflows past the membrane which is typically cellulose. The blood solutescontaining the waste then permeate through the membrane and into thedialysate, a sterilized solution formulated to control solutepermeability through the membrane. Because osmosis may result in theundesirable net transfer of water from the dialysate into the bloodwhich may result in edema, hemodialysis is often utilized in conjunctlonwith ultrafiltration to remove the excess water. The dialysate can beprepared by the combination of purified water, produced by reverseosmosis, and the desired concentrate.

Reverse osmosis using synthetic polymeric membranes has been used for avariety of industrial end products. Such processes include thedesalination of sea water and the processing of food and beverages. Thealternative method of processing is by distillation. However, because ofthe high energy requirements of distillation, reverse osmosis processescompare favorably as the most economic route. Furthermore, for solutionssusceptible to degradation at high temperatures such as fruit juices,reverse osmosis may be the most practical manner of processing thesolutions while preventing substantial loss of desirable components inthe original solutions.

An important use of the reverse osmosis process in the medical field isits application to peritoneal dialysis therapy. A generalized discussionof peritoneal dialysis therapy is discussed and described in U.S. Pat.No. 4,239,041 to Popovich et al. In particular, the Popovich patentdiscusses a fluid infusion method for continuous, ambulatory peritonealdialysis (CAPD). The CAPD process differs from the more popularhemodialysis process in that it utilizes the body's natural peritonealmembrane in order to provide for the function of the artificial kidney.The CAPD process, however, while being ambulatory, is performed duringthe patient's normal, daily routine and requires treatment several timesduring the day. For this reason, the patient must remain by thedialysate supply during the entire period of treatment. This obviouslywill conflict with the patient's daytime activities and/or jobrequirements.

Alternatively, peritoneal dialysis can be performed at a hospital orclinic which requires that the patient visit the facility in order toobtain the required treatment. Such a visit requirement also has itsinherent limitations on the normal activities of the patient.

Peritoneal dialysis is also generally discussed and described in the"Handbook 6010, Automated Peritoneal Dialysis", 1979 which isincorporated herein by reference. This handbook was distributed by B-DDrake Willock, a division of Becton, Dickenson and Co. in New Jersey anddiscusses that dialysate which is prepared from purified water can beinfused into the patient's peritoneum through a catheter. Dialysis ofthe patient's blood through the peritoneal membrane and into thepurified water region then occurs, allowing the body to excrete water,metabolites and toxins, and to regulate fluid, electrolyte and acid-basebalance. The waste dialysate is subsequently drained out of the body.Peritoneal dialysis can be performed by various methods such ascontinuous and intermittent, as explained in Miller et al. "AutomatedPeritoneal Dialysis Analysis of Several Methods of Peritoneal Dialysis",Vol. XII Trans. Amer. Soc. Artif. Int. Organs p. 98 (1966).

Problems related to peritoneal dialysis include the difficulty inmaintaining sterile conditions so as to prevent infection and thecomplexity of operating currently available peritoneal dialysis systems.A peritoneal dialysis device manufactured by Physio-Control Corporationof Redmond, Washington is generally described in "PDS 400 Service ManualP/N 10454-01 July, 1981" which is also incorporated herein by reference.The device purifies the source water using a reverse osmosis modulewhich is formed of a plastic housing containing a spiral wound membraneof cellulose triacetate. The device mixes the purified water withconcentrate to form a dialysate, and then delivers the dialysate to thepatient. The system controls the dialysate delivery at a set inflow rateand period and a set outflow period. An alarm is sounded and the systemis turned off if various parameters are not within the set ranges. Theparameters include the dialysate temperature, the dialysateconductivity, the inflow and outflow volume, and the systemoverpressure. The Physio-Control device is made up of two subsystems;the RO unit and the proportioning and monitoring unit. The device isbulky and complex in operation and requires extensive training of eitherthe medical personnel or the patient that operate it. Additionally,extensive preventive maintenance is required to keep the systemoperational. Such maintenance includes the replacement of the ROpre-filter, filters and O-rings within the device every 500 hours of useas well as the cleaning of the RO sump pump. In addition, the devicerequires cleansing with bleach every 100 hours. Moreover, an extensivedisinfection with formaldehyde must be performed before patient use ifthe sterile path has been broken during the functional test, calibrationor adjustment of the device.

Another peritoneal dialysis device was designed by Ramot Purotech Ltd.The device employs RO membrane filtration through an RO cell formed of alarge number of small membranes supported on plastic plates. Aftermixing the filtered water with concentrate to form the dialysate, thedialysate is fed by gravity to the patient. The outflow from the patientis also done by gravity into a waste bag. The need to connect thedialysate to the patient, leads to difficulties in maintaining sterileconditions.

Yet another peritoneal dialysis system is disclosed in U.S. Pat. No.4,586,920; 4,718,890; and 4,747,822 to Peabody. The patents recite acontinuous flow peritoneal dialysis system and process in which acontinuous flow of sterile dialysis fluid is produced and caused to flowthrough the peritoneal cavity of the patient is a single-pass opencircuit. A gravity fed system is utilized to flow the fluid into thepatient's peritoneum. The pressure of the peritoneum and the volume offluid into the peritoneum are monitored to ensure efficient andcomfortable peritoneal dialysis. The pressure monitors of the system arecapable of controlling the flow of fluid into the peritoneum. Thissystem, however similar to others previously discussed, does not addressthe manner in which sterile conditions may maintained nor the dauntingcomplexity of operation required to be performed by the patient or caregiver to use and maintain the system.

These and other problems have been solved in part by another device forperitoneal dialysis treatment calledeco. the Inpersol Cycler™ 1000, theHandbook of which is incorporated herein by reference. The Cycler™ isused to perform peritoneal dialysis in continuous cycling peritonealdialysis (CCPD) and intermittent peritoneal dialysis (IPD) applications.The Cycler™ 3000 is used to not only perform CCPD and IPD but also tidalperitoneal dialysis (TPD). The Cycler™ is portable and is designed to beused in the home as well as in the clinic or hospital. In typical CCPDapplications the exchanges are made at night while the patient issleeping. A portion of the final dose is retained in the peritoneumduring the day and drained out at beginning of the nightly exchanges.The cycler system includes the cycler control unit and the stand. Thestand holds the cycler unit, and fresh and spent dialysis fluids. Thecycler control unit contains the wagoner, weighing system, valvingsystem and control electronics.

Notwithstanding the Cycler™, the problems of other known peritonealdialysis devices have been solved by the present invention which isdirected to a reverse osmosis (RO) filtration device for purifying waterand for use in a user friendly automatic home dialysis system which willpermit the patient to obtain peritoneal dialysis during sleeping hours.In this fashion, the patient will be free to conduct his normalactivities during his waking or business hours without the interferenceof dialysis treatment. Additionally, the RO device and system of thepresent invention provide a self-contained, compact and sophisticatedsystem whereby peritoneal dialysis is automatically performed andcontinuously controlled so as to allow the patient to undergo peritonealdialysis at home with minimal need for patient intervention. Thispermits the patient to lead a more natural and fuller life thanpermitted under known treatment procedures.

The RO device and system of the present invention also provide for a lowcost, efficient means to produce solutions of sufficient sterility, lowpyrogen content and low dissolved mineral content for many otherindustrial and medical applications. Because of the compactness of theapparatus and its ease of use, purified fluids such as sterile andpyrogen-free water can be produced on site as needed without theinconvenience and cost of storing large quantities of the purifiedfluid. When applied to purifying water, the invention produces water ofsufficient sterility such that the purified water can be employed inperitoneal dialysis, irrigation of patients during surgery orpostoperative therapy, and pharmaceutical production for oral andintravenous administration. Additionally, the RO device can producesterile water for the formulation of dialysate solution required inhemodialysis treatment. The purified water as produced by the device andsystem of the present invention can satisfy U.S.P. requirements aspresented in the United States Pharmacopeia, The National FormularyP1456-1574, 1596-1598, 1705-1710, Jan. 1, 1990, US PXXII United StatesPharmacopeial Convention, Inc. Also, the RO device and system avoids anyneed for terminal sterilization as required by known peritoneal dialysisdevices.

Alternatively, the RO device and system of the present invention may beadapted to supply sterile water for the formulation of dialysate for usein hemodialyzers. The hemodialyzers in turn use the dialysate to purifythe patient's blood in a manner currently used in hospitals and clinics.

For less demanding processes where sterility is not a major concern, theRO device and/or system of the present invention may be adapted todialysis and ultrafiltration processes. Typical end use applicationsinclude those previously discussed such as the recovery of spent causticor acid solutions from industrial production liquors (i.e. rayon steepliquor and metallurgical liquor).

The present invention is also directed toward the method ofmanufacturing the RO device in a manner which would minimize the cost ofmanufacturing and expedite it as well. Assembly steps include theapplication of adhesive in an automated manner by roller coating,induction bonding, sonic welding, and radiation sterilization.

SUMMARY OF THE INVENTION

The present invention is directed to an apparatus for purifying fluidfrom a source comprising first reverse osmosis means adapted for fluidcommunication with the source for purification of at least a portion ofthe fluid from the source; and second reverse osmosis means being influid communication with the first reverse osmosis means to receive atleast some of the purified portion of fluid for further purification ofat least a further portion of the fluid.

The fluid may be in the liquid or gaseous state. The configuration ofthe reverse osmosis means includes reverse osmosis multilayer assemblieswhich are either spirally wound or stacked in a parallel leafconfiguration. Alternatively, the reverse osmosis means is in the formof hollow non-porous semipermeable membrane fibers composed of syntheticmerane. Synthetic membranes useful for reverse osmosis include cellulosenitrate, cellulose acetate, polyamides, polyimides,polytetrafluoroethylene, poly-(vinyl chloride) and polysulfone.

Preferably the RO apparatus is for use with a potable water source andthe first reverse osmosis means comprises a first reverse osmosismultilayer assembly spirally rolled about a first axis so as to providea generally spiral flow path of the water from the source. The secondreverse osmosis multilayer assembly is spirally rolled about a secondaxis so as to provide a generally spiral flow path for at least some ofthe purified first portion of water from the first reverse osmosismeans.

Preferably, the first and said second reverse osmosis multilayerassemblies are formed integrally and the first axis and the second axisare co-linear. A separator means is disposed so as to fluidly separatethe integral multilayer assembly when rolled about its axis into thefirst and the second reverse osmosis multilayer assemblies.

In one embodiment, the separator means is an impermeable adhesive. Alsothe integral multilayer assembly comprises first reverse osmosismembrane layer; porous mesh layer; second reverse osmosis membranelayer; and porous permeate layer. A container can enclose either thefirst or the second reverse osmosis multilayer assembly.

In an alternative embodiment, the first reverse osmosis means isdisposed in an interleaf configuration with the second reverse osmosismeans and each comprises at least a reverse osmosis multilayer assemblyspirally rolled about a common axis. Preferably, the first reverseosmosis multilayer assembly comprises first reverse osmosis membranelayer; porous mesh layer; second reverse osmosis membrane layer; andfirst porous permeate layer. The second reverse osmosis multilayerassembly comprises third reverse osmosis membrane layer; second porouspermeate layer; fourth reverse osmosis membrane layer; and third porouspermeate layer.

The present invention is also directed to a method for purifying fluidfrom a source comprising passing fluid from the source through a firstreverse osmosis means being in fluid communication with the source so asto purify at least a portion of the fluid from the source; and passingthe purified first portion of fluid through a second reverse osmosismeans being in fluid communication with the first reverse osmosis meansto receive the purified portion of water for further purification of thefluid. Preferably the fluid can be water.

According to another embodiment, the present invention is directed to anapparatus for purifying water from a source comprising housing having aninlet for passage of water from a source, a first outlet for passage ofpurified water from the housing and a second outlet for passage of wastewater remaining after purification; first reverse osmosis means disposedwithin said housing and being in fluid communication with the inlet forpurification of at least a first portion of the water from the source;the first reverse osmosis means also being in fluid communication withthe second outlet for passage of waste water through the second outlet;chemical purification means being in fluid communication with the firstreverse osmosis means to receive the first purified portion of water andfor removal of at least chemical contaminants from the first purifiedportion of water; and second reverse osmosis means being in fluidcommunication with the chemical means to receive the chemically purifiedwater for purification of at least a second portion of the chemicallypurified water, the second reverse osmosis means also being in fluidcommunication with the first outlet so as to permit passage of thesecond portion of purified water through the first outlet.

In one embodiment, the housing further comprises a third outlet forpassage of waste water remaining after purification, and the firstreverse osmosis means is in fluid communication with the third outlet soas to permit passage of waste water through the third outlet. The secondreverse osmosis means is in fluid communication with the second outletso as to permit passage of waste water through the second outlet.

The housing is formed of a material possessing sufficient structuralintegrity to withstand the pressure requirements of the reverse osmosisprocess. The material may be but is not limited to steel, aluminum,fiberglass and Kevlar™. Also, the housing includes an elongated hollowcylindrical container having a base and an open end and includes a capconfigured and dimensioned to seal the open end in a fluid tightconfiguration. The cap has an inlet passageway for admitting water fromthe source, a first passageway for purified water and a secondpassageway for waste water. A third outlet passageway could also beprovided for passage of waste water. A generally cylindrical core isdisposed within the housing and extends from the base to the cap. Theintegral multilayer assembly is rolled about the outer surface of thecylindrical core so as to provide for spiral flow paths of the water tobe purified. The cylindrical core has a hollow central portion and thechemical means is disposed within the hollow central portion. Thechemical means includes but is not limited to diatomaceous earth, clay,ion exchange resins, activated carbon or other similar material andmixtures thereof. The chemical means provides a variety of functionsincluding the removal of dissolved gases and chloramine contaminants.Filter plugs are disposed at the ends of the hollow central portion soas to contain the chemical means therebetween. The apparatus furthercomprises a second cylindrical hollow container having a base and anopen end and is configured and dimensioned so as to be adapted to bepositioned within the first container and to receive and to seal thesecond reverse osmosis means therein. At least one 0 ring or othersealing means is disposed between the open end of the second cylindricalhollow container and the impermeable adhesive disposed along the centralportion of the integral multilayer assembly so as to aid in sealing thefirst osmosis means within the second container.

Preferably, the integral multilayer assembly comprises first reverseosmosis membrane layer; porous mesh layer; second reverseosmosis-membrane layer; and porous permeate layer. Also, the first andsaid second reverse osmosis membrane layers each comprises nonporoussemipermeable membrane layer; porous ultrafiltration layer; and poroussupport layer. The semi-permeable membrane layer is formed generally ofa solid nonporous continuous thin polymeric composition and the poroussupport layer is formed generally of polyamide which can be either of awoven or non-woven configuration.

After being rolled about the outer surface of the cylindrical core, thereverse osmosis multilayer assembly generally includes in a radiallyoutwardly configuration from the surface, the porous permeate layer, thesecond reverse osmosis membrane layer, the porous mesh layer and thefirst reverse osmosis membrane layer. Preferably, the nonporoussemi-permeable membrane layers of the first and the second reverseosmosis membrane layers are disposed adjacent the porous mesh layer.

In another preferred embodiment of the present invention, the apparatushas a second reverse osmosis means being in fluid communication with thefirst reverse osmosis means to receive the first purified portion ofwater for purification of at least a second portion of the purifiedwater, the second reverse osmosis means also being in fluidcommunication with the second outlet for passage of waste water throughthe second outlet. Chemical means in fluid communication with the secondreverse osmosis means receives the second purified portion of water andremoves at least chemical contaminants from the second purified portionof water. The chemical means is also in fluid communication with thefirst outlet so as to permit passage of the second portion of purifiedwater through the first outlet.

In another embodiment, the first reverse osmosis means is disposed in aninterleaf configuration with the second reverse osmosis means. The firstreverse osmosis means comprises at least a first reverse osmosismultilayer assembly and the second reverse osmosis means comprises atleast a second reverse osmosis multilayer assembly. Both the first andthe second reverse osmosis multilayer assemblies are spirally rolledabout a common axis. The first reverse osmosis multilayer assemblycomprises first reverse osmosis membrane layer; porous mesh layer;second reverse osmosis membrane layer; and first porous permeate layer.Also, the second reverse osmosis multilayer assembly comprises thirdreverse osmosis membrane layer; second porous permeate layer; fourthreverse osmosis membrane layer; and third porous permeate layer.

Preferably, the first, second, third and fourth reverse osmosis membranelayers each comprises nonporous semi-permeable membrane layer; porousultrafiltration layer; and porous support layer. The semi-permeablemerane layer is formed generally of a solid nonporous continuous thinpolymeric composition such as polyamide. The porous support layer can bemade of polyamide. The polyamide can be of a woven or non-wovenconfiguration.

After the reverse osmosis multilayer assemblies are rolled about theouter surface of the cylindrical core, they include in a radiallyoutwardly configuration from the surface, the third porous permeatelayer, the fourth reverse osmosis membrane layer, the second porouspermeate layer, the third reverse osmosis membrane layer, the firstporous permeate layer, the second reverse osmosis membrane layer, theporous mesh layer and the first reverse osmosis membrane layer.

The nonporous semi-permeable membrane layers of the first and the secondreverse osmosis membrane layers are disposed adjacent the porous meshlayer. Preferably, the nonporous semi-permeable membrane layers of thethird and the fourth reverse osmosis membrane layers are disposedadjacent the second porous permeate layer.

In an alternative embodiment for purifying water from a source, themethod comprises passing water from the source through a first reverseosmosis means being in fluid communication with the source so as topurify at least a first portion of the water from the source; passingthe purified first portion of water through chemical means being influid communication with the first reverse osmosis means to receive thefirst purified portion of water and for removal of at least chemicalcontaminants from the first purified portion of water; and passing thechemically purified water through a second reverse osmosis means beingin fluid communication with the chemical means to receive the chemicallypurified water for purification of at least a second portion of thechemically purified water, the second reverse osmosis means also beingin fluid communication with the first outlet and the second outlet so asto permit passage of the second portion of purified water through thefirst outlet and for passage of waste water through the second outlet.

In yet another preferred embodiment, after passing water from the sourcethrough a first reverse osmosis means so as to purify at least a firstportion of the water from the source, the method comprises passing thepurified first portion of water through a second reverse osmosis meansbeing in fluid communication with the first reverse osmosis means toreceive the purified first portion of water for further purification ofat least a second portion of the water; and passing the purified secondportion of water through chemical means being in fluid communicationwith the second reverse osmosis means to receive the second purifiedportion of water and for removal of at least chemical contaminants fromthe purified second portion of water, the chemical means also being influid communication with the first outlet so as to permit-passage of thechemically purified water through the first outlet. If desired, thepurified water can be passed through a filtration means for furtherpurification.

The present invention also is directed to a peritoneal dialysis systemfor treating a patient comprising reverse osmosis device for purifyingwater from a source and having input means for coupling to the source ofwater; first reverse osmosis means being in fluid communication with theinput means for purification of at least a first portion of the waterfrom the source; and second reverse osmosis means being in fluidcommunication with the first reverse osmosis means to receive thepurified first portion of water for further purification of at least asecond portion of the water; means for supplying a predetermined amountof drug and means for mixing the purified second portion of the fluidwith the concentrate to provide a dialysate solution; and means fordelivering the dialysate solution to the peritoneal cavity of thepatient.

The system further comprises means for draining waste water from thereverse osmosis device and also means for draining spent dialysatesolution from the peritoneal cavity of the patient.

The delivering means can be adapted to include, but not be limited to,continuous, intermittent, tidal or continuous ambulatory peritonealdialysis treatment of the patient as well as other treatments includinghemodialysis.

The system further comprises means for heating the water from thesource. The water can be heated up to about 70° C., preferably up toabout 50° C., for example up to 36° C., to increase the efficiency ofthe reverse osmosis device. The heating means is coupled to the inputmeans of the reverse osmosis device so as to heat the water beforepurification. A high pressure pump can be fluidly coupled between theheater means and the reverse osmosis device so as to provide sufficientpressure to allow for proper operation of the reverse osmosis device.The reverse osmosis device further includes a first outlet for passageof purified water from the second reverse osmosis means and a secondoutlet for passage of waste water remaining after purification. Thereverse osmosis device can further comprise a third outlet in fluidcommunication with the first reverse osmosis means so as to permitpassage of waste water through the third outlet.

Also, a heat exchanger means can be fluidly coupled to the second outletof the reverse osmosis device and can be disposed in thermalrelationship with the water from the source so as to provide fortransfer of heat from the waste water to the water to be heated. Alsoheat exchanger means can be fluidly coupled to the means for drainingspent. dialysate solution and disposed in thermal relationship with thewater from the source so as to provide for transfer of heat from thesolution to the water to be heated. The supplying means comprises astorage bag having a coupling end and containing a predetermined drugand a metering system such as a syringe, or a precision pump in fluidcommunication with the coupling end of the storage container to receivea predetermined amount of drug and also is in fluid communication withthe purified second portion of the water after passing through the firstoutlet.

The system further comprises means for sterilizing the coupling end ofthe storage container when being coupled and decoupled to the meteringsystem.

The mixing means is in fluid communication with the first outlet and themetering means so as to receive the purified second portion of the waterand the predetermined amount of drug for preparation of a dialysatesolution. The mixing means can be any of an ultrasonic,electromechanical, electromagnetic or static mixer.

In one alternative embodiment, the delivery means comprises a dual lumencatheter affixed to the patient and adapted for fluid communication atone end of one lumen with the peritoneal cavity of the patient and atthe other end of the one lumen with the mixing means so as to allow fordelivery of the dialysate solution to the peritoneal cavity. The otherlumen is adapted for fluid communication with the peritoneal cavity ofthe patient at one end and at the other end with a drain means toreceive the spent dialysate solution from the peritoneal cavity.

In another embodiment, the delivery means comprises a single lumencatheter affixed to the patient and adapted for fluid communication atone end of the lumen with the peritoneal cavity of the patient and atthe other end of the lumen with the mixing means so as to allow fordelivery of the dialysate solution to the peritoneal cavity. A pump canbe fluidly coupled, as desired, between the supplying means and thereverse osmosis device, between the mixing means and the peritonealcavity of the patient, and between the peritoneal cavity of the patientand an isolation valve and a drain means for receiving the useddialysate solution. Also, a computer can be employed for predetermined,selective and automatic control of the delivery means. The system canfurther comprise chemical means positioned in fluid communication withthe second reverse osmosis means to receive said second purified portionof water and for removal of at least chemical contaminants from thesecond purified portion of water.

A method for treating a patient comprises purifying water from a sourcewith a reverse osmosis device having input means for coupling to thesource of water; first reverse osmosis means being in fluidcommunication with the input means for purification of at least a firstportion of the water from the source; and second reverse osmosis meansbeing in fluid communication with the first reverse osmosis means toreceive the purified first portion of water for further purification ofat least a second portion of the water; supplying a predetermined amountof drug; mixing the drug with the purified second portion of the waterso as to provide a dialysate solution; and delivering the dialysatesolution to the peritoneal cavity of the patient. The delivery of thedialysate solution can be continuous, intermittent, of the tidal mode oftreatment or of the continuous ambulatory mode of treatment. Preferably,the water is heated and is pumped under a predetermined pressure priorto purification.

Also, at least a portion of the waste water from the reverse osmosisdevice can be returned to a heat exchanger means disposed in thermalrelationship with the water from the source so as to provide fortransfer of heat from the waste water to the water to be heated. Atleast a portion of the spent dialysate solution can be returned to aheat exchanger means disposed in thermal relationship with the waterfrom the source so as to provide for transfer of heat from the dialysatesolution to the water to be heated. Moreover, the first purified portionof water can be passed through chemical means being in fluidcommunication with the first reverse osmosis means for removal of atleast chemical contaminants from the first purified portion of waterbefore passing on to the second reverse osmosis means. Alternatively,the second purified portion of water can be passed through chemicalmeans being in fluid communication with the second reverse osmosis meansfor removal of at least chemical contaminants from the second purifiedportion of water. Also the chemically treated water portion can bepassed through a filtration means fluidly coupled to the chemical meansfor further purification of the water portion. The method furthercomprises draining waste water from the reverse osmosis device. Also themethod can further comprise draining spent dialysate solution from theperitoneal cavity of the patient. Another system for supplying purifiedwater from a source comprises a reverse osmosis device according to thepresent invention and means for delivering the purified second portionof the water to either a storage means for future use or to a controlmeans for immediate predetermined use.

The present invention is moreover directed to a hemodialysis system fortreating a patient comprising reverse osmosis device for purifying waterfrom a source and having input means for coupling to the source ofwater; first reverse osmosis means being in fluid communication with theinput means for purification of at least a first portion of the waterfrom the source; and second reverse osmosis means being in fluidcommunication with the first reverse osmosis means to receive thepurified first portion of water for further purification of at least asecond portion of the water; and means for supplying a predeterminedamount of drug; means for mixing the purified second portion of thewater with the drug to provide a dialysate solution; and means fordelivering the dialysate solution to a hemodialyzer. The system furthercomprises means for draining waste water from the reverse osmosis deviceand also means for draining spent dialysate solution from thehemodialyzer. The reverse osmosis device further comprises chemicalmeans being in fluid communication with the first reverse osmosis meansto receive the first purified portion of water and for removal of atleast chemical contaminants from the first purified portion of waterbefore passing on to the second reverse osmosis means. Means for heatingthe water from the source is provided and is coupled to the input meansof the reverse osmosis device so as to heat the water beforepurification. A high pressure pump is fluidly coupled between the sourceand the reverse osmosis device so as to provide sufficient pressure toallow for proper operation of the reverse osmosis device. The systemfurther comprises means for heating the water from the source which isfluidly coupled between the high pressure pump and the source so as toheat the water before purification. The means for heating the water fromthe source can also be fluidly coupled between the high pressure pumpand the reverse osmosis device so as to heat the water beforepurification. The reverse osmosis device further includes a first outletfor passage of purified water from the second reverse osmosis means anda second outlet for passage of waste water. The reverse osmosis devicefurther comprises a third outlet for passage of waste water. Theapparatus first osmosis means is in fluid communication with the thirdoutlet so as to permit passage of waste water through the third outlet.The second reverse osmosis means is in fluid communication with thesecond outlet for passage of waste water through the second outlet. Aheat exchanger means is fluidly coupled to the second and/or thirdoutlet of the reverse osmosis device and is disposed in thermalrelationship with the water from the source so as to provide fortransfer of heat from the waste water to the water to be heated.Alternatively, the heat exchanger means can be fluidly coupled to themeans for draining spent dialysate solution and disposed in thermalrelationship with the water from the source so as to provide fortransfer of heat from the solution to the water to be heated.

According to the system, the supplying means comprises a storagecontainer having a coupling end and containing a predetermined drug, anda metering system in fluid communication with the coupling end of thestorage container to receive a predetermined amount of drug and isfurther in fluid communication with the purified second portion of thewater after passing through the first outlet. The system furthercomprises means for sterilizing the coupling end of the storagecontainer when being coupled and decoupled to the metering system. Themixing means is in fluid communication with the first outlet and themetering system so as to receive the purified second portion of thewater and the predetermined amount of drug for preparation of adialysate solution. The mixing means can be an ultrasonic,electromagnetic, electromechanical or a static mixer. Pump means isfluidly coupled between the supplying means and the reverse osmosisdevice. Pump means can also be fluidly coupled between the mixing meansand the hemodialyzer, and also between the hemodialyzer and a drainmeans for receiving the spent dialysate solution. A computer meansprovides for predetermined, selective and automatic control of thedelivery means, the supplying means, the mixing means and the drainingmeans.

The present invention is also directed to a system for irrigating aportion of a patient's body comprising a reverse osmosis deviceaccording to the present invention and means for supplying the purifiedsecond portion of the water to the portion of the patient's body. Thesystem can further comprise means for supplying a predetermined amountof drug; means for mixing the purified second portion of the water withthe drug to provide a drug solution; and means for delivering the drugsolution to the portion of the patient's body. The supplying means isadapted for irrigating a wound or a cavity of a patient with the drugmixture. The supplying means can also include a humidifying means whichis adapted for humidification of a patient's lungs.

In addition, the present invention is directed to a system for deliveryof a predetermined injectable drug to a patient comprising a reverseosmosis device according to the present invention; means for supplyingand mixing the predetermined drug with the purified second portion ofwater; and means for supplying the said drug and purified water mixtureto a body portion of the patient.

A heat exchanger according to the present invention for transferringheat to a first source of fluid from a second source of fluid comprisesan elongated core; first film composite having a first porous mesh and afirst fluidly impermeable layer; second film composite having a secondporous mesh and a second fluidly impermeable layer; the first and thesecond film composites being disposed in an interleaf configuration andbeing disposed about the core so as to provide a first fluid flow pathgenerally between the core and the first fluidly impermeable layer and asecond fluid flow path between the first fluidly impermeable layer andthe second fluidly impermeable layer such that heat from fluid in one ofthe first and the second flow paths can be transferred to the fluid inthe other flow path.

The core is generally cylindrical and the first and the second filmcomposites are generally rectangular and are spirally rolled about thecore. The first and the second fluidly impermeable layers are eachformed of a metallic foil, an impermeable polymeric film, or animpermeable inorganic film. The heat exchanger further comprises meansfor fluidly sealing the first and the second film composites along oneedge to the core and also sealing to the core the adjacent edgestransverse to the one edge. Preferably the sealing means comprises animpermeable adhesive. The heat exchanger further comprises an elongatedhollow cylindrical housing container having a base and an open end. Thehousing container includes a cap configured and dimensioned to fluidlyseal the open end and includes an inlet passageway for admitting fluidfrom the first source, a first outlet for passage of the first sourceafter heating, a second inlet for passage of said second source and asecond outlet for passage of the second source after transfer of heat tothe first source.

In one embodiment, the first inlet and the first outlet are in fluidcommunication with the first fluid path, and the second inlet and secondoutlet are in fluid communication with the second fluid path.

A peritoneal dialysis system according to the present invention fortreating a patient comprises a reverse osmosis device for purifyingwater according to the present invention wherein the reverse osmosisdevice is formed of radiation sterilizable components; means forsupplying a predetermined amount of drug; means for mixing the purifiedsecond portion of the water with the drug to provide a dialysatesolution; and means for delivering the dialysate solution to theperitoneal cavity of the patient. The supplying means is selectivelyreplaceable in the system and is adapted for maintaining sterile fluidcouplings and decouplings in the system. Similarly, the mixing means anddelivering means are adapted for maintaining sterile fluid couplings anddecouplings in the system. The system further comprises means fordraining spent dialysate solution from the peritoneal cavity of thepatient. The draining means includes a one way isolation valve toprevent any retrograde biocontamination of the peritoneal cavity of thepatient.

In one embodiment, the supplying means comprises a storage containerhaving a coupling end and containing a predetermined drug, and ametering system in fluid communication with the coupling end of thestorage container to receive a predetermined amount of drug and furtheris in fluid communication with the purified second portion of the waterafter passing through the first outlet. The system further comprisesmeans for sterilizing the coupling end of the storage container whencoupled and decoupled to the metering system. Preferably, the mixingmeans is in fluid communication with the first outlet and the meteringsystem so as to receive the purified second portion of the water and thepredetermined amount of drug for preparation of a dialysate solution.The system further comprises first pump means fluidly coupled betweenthe mixing means and the reverse osmosis device, second pump meansfluidly coupled between the mixing means and the supplying means, thirdpump means adapted to be fluidly coupled between the mixing means andthe peritoneal cavity of the patient and fourth pump means adapted forfluid coupling between the peritoneal cavity of the patient and a drainmeans for receiving the used dialysate solution. The first, second,third and fourth pump means comprise volumetric pumps which arecalibratable. A second supplying means is adapted for fluid coupling tothe peritoneal cavity of the patient for selective admission of a secondpredetermined drug. A fifth pump means is adapted for fluid couplingbetween the-second supplying means and the peritoneal cavity of thepatient. Also, the fifth pump means comprises a volumetric calibratablepump.

The system further comprises clamp means for selective and independentoperation of the components of the system. The clamp means comprises aplurality of on-off clamps disposed at predetermined fluid positions ofthe system. A computer means is coupled to the plurality of on-offclaims for automatic predetermined operation thereof.

The housing of the reverse osmosis device includes an elongated hollowfirst cylindrical container having a base and an open end. A generallycylindrical core is disposed within the housing and extends from thebase to the cap. The first and second reverse osmosis means are rolledabout the outer surface of the cylindrical core so as to provide forspiral flow paths of the water to be processed. The cylindrical core hasa hollow central portion for receiving chemical means within the hollowcentral portion. The system further comprises a second cylindricalhollow container having a base and an open end and which is configuredand dimensioned so as to be adapted to be positioned within the firstcontainer, and to receive and to seal the first reverse osmosis meanstherein. The housing includes a cap configured and dimensioned tofluidly seal the open end and includes an inlet passageway for admittingwater from the source, a first outlet passageway for purified water anda second outlet passageway for waste water. The cap has an inner faceand an outer face and further comprises a plurality of protrusionsextending from the inner face into selective contacting relationshipwith the core at predetermined positions. The protrusions are fusablewith the core upon application of at least one of ultrasonic and thermalenergy. Also, the second cylindrical container has an inner face andfurther comprises a plurality of protrusions extending from the innerface into selective contacting relationship with the core atpredetermined positions. The core has a plurality of passagewayspredeterminately coupled through the inner face of the cap and the innerface of the second container to provide fluid flow paths for the waterfrom the source, the waste water and the purified water into, throughand out of the housing.

The system comprises at least a first conductivity sensor disposeddownstream of said source of purified water for monitoring of theconductivity of said water. A second conductivity sensor is disposeddownstream of the mixing means for monitoring of the conductivity of thedialysate solution.

The system further comprises means for restricting the flow of watertherethrough and also thereby through the reverse osmosis device. Theflow restricting means comprises a flow plug configured and dimensionedso as to be adapted to be disposed within at least one passageway in thecore. The flow plug has a reduced effective cross sectional area thanthe at least one passageway so as to restrict the flow of water throughthe passageway and provide for predetermined pressures on either side ofthe flow plug. Preferably, at least two flow plugs are disposed in adifferent passageway in the core. A computer means is coupled to thefirst and the second conductivity sensors for selective, predeterminedoperation of the system.

A method of manufacturing a reverse osmosis device on a core forpurifying water from a source comprises providing an integral reverseosmosis multilayer assembly having first reverse osmosis membrane layer;porous mesh layer; second reverse osmosis membrane layer; and porouspermeate layer; sealing a central portion of the integral multilayerassembly; sealing at least one edge of the multilayer assembly to thecore; sealing along two opposed side edges of the integral multilayerassembly; rolling the integral multilayer assembly in a spiralconfiguration on the core; and bonding the seals by induction heating soas to fluidly seal the integral multilayer assembly along the edges andthe central portion and so as to separate the integral multilayerassembly into a first reverse osmosis multilayer assembly and a secondreverse osmosis multilayer assembly. In one embodiment, sealing isobtained by disposing an impermeable adhesive along the length of acentral portion of the integral multilayer assembly; and disposing animpermeable adhesive along the side edges of the integral multilayerassembly.

The method further comprises enclosing the spirally rolled and bondedintegral multilayer assembly in a housing having an inlet for passage ofwater for a source, a first outlet for passage of purified water fromthe passage of purified water from the housing and a second outlet forpassage of waste water remaining after purification, disposing the firstreverse osmosis multilayer assembly within the housing in fluidcommunication with the inlet for purification of at least a firstportion of the water from the source, and disposing the second reverseosmosis multilayer assembly within the housing in fluid communicationwith the first reverse osmosis means to receive the first purifiedportion of water for purification of at least a second portion of thepurified water, the second reverse osmosis means also being disposed influid communication with the second outlet for passage of waste waterthrough the second outlet.

Alternatively, the method can comprise providing an integral reverseosmosis multilayer assembly having first reverse osmosis membrane layer;first porous mesh layer; second reverse osmosis membrane layer; porouspermeate layer; third reverse osmosis membrane layer; second porouspermeate layer; fourth reverse osmosis membrane layer; and third porouspermeate layer.

The present invention is also directed to a device for sterile couplingand decoupling of a drug container to a delivery system, the containerhaving an open end and a puncturable seal adapted for entry into theopen end so as to seal the open end comprising a housing configured anddimensioned for receiving and cooperating with the plug so as to providea fluid tight cooperating engagement when the plug enters the housing;barrier means disposed within the housing and having a portion thereofadapted for sterile penetration of the barrier means by a conduit of thedelivery system; an inlet duct and an outlet duct disposed through thehousing and disposed between the barrier means and the plug whenpositioned within the housing. The inlet duct is adapted for fluidcoupling to a source of sterilizing fluid, and the outlet duct isadapted for fluid coupling to a reservoir container to receive thesterilizing fluid after passing across the portion of the plug facingthe barrier means.

The present invention is also directed to a hemoultrafiltration systemfor treating a patient comprising reverse osmosis device for purifyingwater from a source and having input means for coupling to the source ofwater; first reverse osmosis means being in fluid communication with theinput means for purification of at least a first portion of the waterfrom the source; and second reverse osmosis means being in fluidcommunication with the first reverse osmosis means to receive thepurified first portion of water for -further purification of at least asecond portion of the water; and means for supplying a predeterminedamount of drug; means for mixing the purified second portion of thewater with the drug to provide a blood make up solution; and means fordelivering the blood make up solution to the concentrated blood outletof a hemoultrafilter. The system further comprises means for drainingwaste water from the reverse osmosis device and also means for drainingspent waste solution from the hemoultrafilter. The reverse osmosisdevice further comprises chemical means being in fluid communicationwith the first reverse osmosis means to receive the first purifiedportion of water and for removal of at least chemical contaminants fromthe first purified portion of water before passing on to the secondreverse osmosis means. Means for heating the water from the source isprovided and is coupled to the input means of the reverse osmosis deviceso as to heat the water before purification. A high pressure pump isfluidly coupled between the source and the reverse osmosis device so asto provide sufficient pressure to allow for proper operation of thereverse osmosis device. The system further comprises means for heatingthe water from the source which is fluidly coupled between the highpressure pump and the source so as to heat the water beforepurification. The means for heating the water from the source can alsobe fluidly coupled between the high pressure pump and the reverseosmosis device so as to heat the water before purification. The reverseosmosis device further includes a first outlet for passage of purifiedwater from the second reverse osmosis means and a second outlet forpassage of waste water. The reverse osmosis device further comprises athird outlet for passage of waste water. The apparatus first osmosismeans is in fluid communication with the third outlet so as to permitpassage of waste water through the third outlet. The second reverseosmosis means is in fluid communication with the second outlet forpassage of waste water through the second outlet. A heat exchanger meansis fluidly coupled to the second and/or third outlet of the reverseosmosis device and is disposed in the final relationship with the waterfrom the source so as to provide for transfer of heat from the wastewater to the water to be heated. Alternatively, the heat exchanger meanscan be fluidly coupled to the means for draining spent waste solutionand disposed in thermal relationship with the water from the source soas to provide for transfer of heat from the solution to the water to beheated.

According to the system, the supplying means comprises a storagecontainer having a coupling end and containing a predetermined drug, anda metering system in fluid communication with the coupling end of thestorage container to receive a predetermined amount of drug and isfurther in fluid communication with the purified second portion of thewater after passing through the first outlet. The system furthercomprises means for sterilizing the coupling end of the storagecontainer when being coupled and decoupled to the metering system. Themixing means is in fluid communication with the first outlet and themetering system so as to receive the purified second portion of thewater and the predetermined amount of drug for preparation of a bloodmake up solution. The mixing means can be an ultrasonic,electromagnetic, electromechanical or a static mixer. Pump means isfluidly coupled between the supplying means and the reverse osmosisdevice. Pump means can also be fluidly coupled between the mixing meansand the hemofilter, and also between the hemofilter and a drain meansfor receiving the spent waste solution. A computer means provides forpredetermined, selective and automatic control of the delivery means,the supplying means, the mixing means and the draining means.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention is described in greater detail hereinbelow, withreference to the drawings wherein:

FIG. 1 is a schematic view of an automatic peritoneal dialysis systememploying an RO device according to the present invention.

FIG. 2 is a partial schematic view of the automatic peritoneal dialysissystem of FIG. 1 for use with a single lumen catheter.

FIG. 3 is a partial schematic view of the system of FIG. 1 adapted foruse with a hemodialyzer.

FIG. 4 is a cross sectional view of an RO device according to thepresent invention.

FIG. 5 is a perspective view exposed in part of the RO device of FIG. 4to illustrate generally the internal components and arrangement.

FIG. 6 is a perspective view exposed in part of the RO device of FIG. 4to illustrate the various fluid flow paths.

FIG. 7 is a cross sectional end view taken along the lines 7--7 of FIG.4.

FIG. 8 is a cross sectional view of an alternative embodiment of the ROdevice according to the present invention.

FIG. 9 is a perspective view exposed in part of an alternative RO deviceof FIG. 8 to illustrate generally the internal components andarrangement.

FIG. 10 is a perspective view exposed in part of an alternative ROdevice of FIG. 8 to illustrate the various fluid flow paths.

FIG. 11 is a cross sectional end view taken along the lines 11--11 ofFIG. 8.

FIG. 12 is a front view of the metal top portion of cap for sealing theopen end of the housing of the RO device of FIGS. 4 and 8.

FIG. 12A is an inside view of the plastic portion of the cap of FIG. 12.

FIG. 12B is an inside view of the second pressurized container insidethe housing of the RO device according to the present invention.

FIG. 13 is a transverse cross sectional view of the RO multilayerassembly prior to winding about the core of the RO device of FIGS. 4 and8.

FIG. 14 is an exploded cross sectional view of the RO multilayerassembly of FIG. 13.

FIG. 15 is an exploded cross sectional view of the RO membranes of FIG.14.

FIG. 16 is a cross sectional view of still another embodiment of the ROdevice according to the present invention.

FIG. 17 is a transverse cross sectional view of the formation of the ROmultilayer assembly of the RO device of FIG. 16.

FIG. 18 is a cross sectional view in the opposite direction of FIG. 17of the RO multilayer assembly of the RO device of FIG. 16 in anassembled configuration and illustrating the fluid flow paths.

FIG. 19 is an exploded cross sectional view of the RO multilayerassembly of FIG. 18.

FIG. 20 is a cross sectional view of yet another alternative embodimentof an RO device according to the present invention wherein the inletport is at a different end than the outlet ports.

FIG. 21 is a cross sectional view of still another alternativeembodiment wherein the inlet port is generally transverse to the outletports.

FIG. 22 is a cross sectional view of a portion of a heat exchangeraccording to the present invention.

FIG. 22A is an end view along lines 22A-22A of FIG. 22.

FIG. 23 is a side end view of the first layer of the heat exchangerprior to assembly about the core.

FIG. 24 is a top view of the first layer of FIG. 23.

FIG. 25 is a side end view of the first and second layers of the heatexchanger prior to assembly about the core.

FIG. 26 is top view of the second layer of FIG. 25 with the first layerremoved.

FIG. 27 is a schematic view of an alternative embodiment of apurification system employing an RO device according to the .presentinvention for use in an automatic peritoneal dialysis system or otherapplication uses.

FIG. 28 is a side view of a restrictor for use in the RO deviceaccording to the present invention.

FIG. 28A is a view along lines 28A-28A of FIG. 28.

FIG. 29 is a perspective view of the restrictor of FIG. 27.

FIG. 30 is an exploded side view of an alternative embodiment of arestrictor according to the present invention.

FIG. 31 is an end view of the restrictor assembly of FIG. 30.

FIG. 32 is a perspective view of the application of induction heating toat least a portion of the RO multilayer assembly for heating of theadhesive bond during the assembly of the RO multilayer assembly.

FIG. 33 is an alternative embodiment of an induction heater for use inthe fabrication of the RO multilayer assembly of the RO device accordingto the present invention.

FIG. 34 is a method of sonic welding the cap to the hollow core of theRO device.

FIG. 35 is a method of performing a sterile connection.

FIG. 36 is a partial schematic view of the system of FIG. 1 generallyadapted for use in hemofiltration.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

In the description which follows, any reference to either orientation ordirection is intended primarily for the purpose of illustration and isnot intended in any way as a limitation of the scope of the presentinvention.

The peritoneal dialysis system (PDS) 10 of FIG. 1 of the presentinvention is designed to preferably utilize potable water andprepackaged drug mixtures or concentrate to enable a patient to obtainperitoneal dialysis at home and preferably at night. If desired, othersources of water can be utilized as well. For instance, non-potable tapwater can be used to produce potable water by the RO device which inturn can be utilized by the peritoneal dialysis system.

As shown in FIG. 1, water from a source 12 is admitted optionallythrough preflter 13 to remove particulates which are greater or equal toabout 5 microns in size and through a valve 14 and heat exchanger 16into a heater 18 and thereafter is passed through a high pressure pump20 to the reverse osmosis (RO) device 22 according to the presentinvention. Within the RO device 22, some of the potable water ispurified and exits optionally through a sterilizing filter 23 into asurge container such as a bag 24. The waste water is passed through anon/off clamp 26 to the heat exchanger 16. The heat exchanger 16transfers at least a portion of the heat from the waste water so as towarm the original potable water before the potable water passes throughheater 18. The on/off clamp 28 can regulate the passage of the purifiedpermeate to the surge container 24 and an on/off clamp 30 canalternatively allow for passage of excess permeate to the drain oranother collection container for storage through the isolation one-wayvalve 56.

A conductivity sensor 25 is placed downstream of the RO device 22 tocontinually or periodically monitor-the electrical resistivity of thepurified permeate water. Alternatively, the conductivity sensor may beplaced downstream of on/off clamp 30 to periodically monitor theelectrical resistivity of the purified permeate.

A pump 32 passes the ultrapure water or permeate from the surgecontainer 24 to mixing bags 34 and 36. Concentrate such as a prepareddrug or other desired mixture from sources 38 and 40 passes throughmetering pumps 42 and 44 that pass a predetermined amount of concentrateinto the mixing container 34 and 36 that can mix and measure andalternatively feed to the downstream pump 46. Also, drug sources inaddition to sources 38, 40 can be provided, as desired, or only one maybe utilized if preferred. In a preferred embodiment, source 38 couldinclude a predetermined dextrose solution of about 65% concentrate. Toallow for conductivity monitoring, the dextrose source 38 can beprovided with a predetermined amount of electrolytes that can bemeasured upon coming into contact with conductivity sensor, which willbe discussed in more detail below. Similarly, other sources can beprovided with electrolyte markers that would allow for conductivitymeasurement as well. Of course, to the extent that other sources alreadycontain electrolytes, any additional markers are not required but couldaid in the measurement process. Conductivity sensors 75 and 77 areplaced downstream of mixing bags 34 and 36 respectively so as tocontinually or periodically monitor the electrical resistivity of themixed solutions from the mixing bags. Alternatively a conductivitysensor may be placed downstream of clamp 76 and 78 so as to periodicallymonitor the electrical resistivity of the mixed solutions from themixing bags. The conductivity sensors may also be used to aid in theformulation of the dialysate.

Advantageously, a heater 45 is used to control the temperature of thedialysate within desired ranges.

By means of the high accuracy pump 46, the dialysate is then admittedthrough a dual lumen catheter 48 into a patient's peritoneal cavity 50.Discharge from the patient is provided by a downstream high accuracypump 52 into a discharge measurement container 54 and thereafter,through pump 55 and an isolation one-way valve 56, which serves as abarrier against virus, bacteria and pyrogen, to a drain 58.Alternatively, with the on/off clamp 84 closed and on/off clamp 86opened, the discharge from the patient passes through the heat exchanger16 to transfer at least a portion of the heat from-the discharge so asto warm the original potable water before the potable water passesthrough heater 18. The discharge is subsequently drained off throughisolation one-way valve 56 to drain 58.

The surge container 24 is optionally supported by hook means 60 which isconnected to weight measurement mechanism 64. The discharge measurementcontainer 54 is supported by hook means 62 which is connected to weightmeasurement mechanism 66. In one preferred embodiment, the weightmeasurement mechanisms provide electrical signals corresponding to theweight of the contents of the respective container. These signals aretransmitted to a computer control system (not shown in FIG. 1) that isdiscussed in greater detail below.

As shown in FIG. 1, an outlet through on/off clamp 71 is providedupstream of the mixing containers 34 and 36 for flushing, priming andcalibrating. Additional clamps 72 and 74 are provided to close off thedownstream flow paths when clamp 71 is opened. In this manner, thepermeate or ultrapure water combining with concentrate from sources 38and 40 can initially be passed through isolation valve 56 to drain untilproper operation and priming is obtained. Thereafter, clamp 71 is closedand clamps 72 and/or 74 are opened according to the desired operation.When clamps 72 and 74 are closed and clamp 71 is left open, thedischarge measurement container 54 along with the hook means 62 andweight measurement mechanism 66 can then be used to calibrate thedelivery rate of the pumps 32, 42 and 44 individually. Similarly, whenclamp 47 is opened and clamp 49 is closed, the discharge measurementcontainer 54 along with the hook means 62 and weight measurementmechanism 66 can be used to calibrate pumps 46 and 80 individually. Whenboth clamps 47 and 49 are closed, calibration of pump 52 can beperformed. Other on/off clamps 76 and 78 control the outflow from mixingcontainers 34 and 36.

The on/off clamp 86 and pump 55 control the flow of the discharge fromthe discharge measurement container 54 to the heat exchange 16 andisolation one-way valve 56. Alternatively, with clamp 86 closed, thedischarge can flow through pump 55 and clamp 84 to the isolation one-wayvalve 56 to drain 58.

Within the mixing containers 34 and 36, the concentrate and permeate areadequately mixed to provide a dialysate solution suitable for theperitoneal dialysis treatment of the patient 50. The mixing can beperformed by known methods which include, for example, ultrasonic,mechanical, static and also electromechanical modes of mixing. Onepreferred embodiment of mixing apparatus is of the electromechanicaltype and is described in greater detail below.

Optionally, a container 82 and pump 80 are connected just upstream ofclamp 49 to provide a method of administering drugs into the patient 50.Such drugs include but are not limited to insulin, heparin, antibiotics,erythro poietin, and nutritional supplements like calcium, magnesium andamino acids.

The dual lumen catheter 48 is of a configuration that is surgicallyimplanted into the patient 50 and extends into the peritoneal cavity byappropriate lumen tubing (not shown) as is well known to those in themedical art. One lumen is coupled to the pump 46 while the other lumenis coupled to discharge pump 52.

In operation, potable water such as from a tap, is passed through valve14, warmed to the desired temperature by heat exchanger 16 and heater 18and pumped under pressure through pump 20 into RO device 22. Some of thetap water is purified and sterilized so as to be free of pyrogens and tohave an electrical resistivity of greater than approximately 0.05megaohms per centimeter, which corresponds to about 25 ppm dissolvedsolids content, as determined by conductivity sensors. Waste water exitsthrough clamp 26 and goes into the heat exchanger 16. The purified wateror permeate is optionally passed through a sterilizing filter (i.e., .22micrometer (μm) filter) and then admitted into a surge container 24where it is optionally measured and stored, as desired, until pumped outby pump 32 into mixing containers 34 and/or 36. Also, concentrate of aprepared drug and treatment mixture, in paste, liquid or solid form ispremeasured in source 38 and 40 and advanced by metering device such aspumps 42 and 44 or other delivery techniques or methodologies into theflow path passing with the permeate into the mixing containers 34 and/or36. After suitable mixing the dialysate solution in mixing containers 34and/or 6 is pumped into the patient 50 by pump 46 through one lumen ofthe dual lumen catheter 48. Optionally, drugs may be administered to thepatient 50 by pumping the drugs from containers 82 into the line justupstream of the catheter. In a continuous mode of operation, the wastedialysate is pumped from the peritoneal cavity through pump 52 to thedrain 58 or alternatively to heat exchanger 16 before being releasedthrough drain 58. The PDS system 10 of the present invention can also beoperated for intermittent and tidal modes of peritoneal dialysistreatment, as desired. In some modes, the dual lumen catheter 40 can bereplaced at points A and B with a single lumen catheter in accordancewith known procedures as shown in FIG. 2.

Where the present system is adapted to supply sterile dialysate for usewith a hemodialyzer 300, the catheter is replaced at points A and B byfluid connections to a hemodialyzer 300 as shown in FIG. 3. Meteringpumps 302 and 304 are used to flow the patient's blood into and out ofthe hemodialyzer 300. Alternatively, the catheter can be replaced atpoints A and B by fluid connections to a hemoultrafilter 900 as shown inFIG. 36. Metering pumps 902 and 904 are used to flow the patient's bloodinto and out of the hemoultrafilter 900. A general description ofhemofiltration of blood is presented in "Handbook of Dialysis", Little,Brown and Company, Boston/Toronto (1988) at pages 144-45 which areincorporated herein by reference. In the course of hemofiltrationtreatment, about 25 to 120 liters of blood make up solution will besupplied from point A in FIG. 36 to be combined with the concentratedblood exiting from the hemoultrafilter device 900. Waste solution exitsfrom the hemoultrafilter device at point B.

The flow paths shown in FIG. 1 are provided by tubing well known tomedical personnel. However, the tubing or flow paths downstream of theRO device 22 and through to the catheter 48 are maintained preferably ina sterile condition. For this reason, connections or couplings of thetubings and the various components of the PDS system 10 are kept sterileas well. Preferably, these flow paths including the RO device areprovided in a modular compartment, as described in greater detail below,so that the patient need only replace the module compartment whennecessary to replenish the RO device or the concentrate. The RO deviceitself is sterilized by radiation. Likewise, the concentrate issterilized by terminal sterilization or by a sterile filling techniqueas taught, for example, in U.S. patent application Ser. No. 07/510,317,R. J. Kruger, et al. filed Apr. 17, 1990 for "Method for Sterilizing andEnclosure with Non-Condensing Hydrogen Peroxide-Containing Gas", whichis incorporated herein by reference. Alternatively, a sterile connectingtechnique described in FIG. 35 may be used for connecting containers 38,40 and 82 to the system as shown in FIG. 1. As shown in FIG. 35, a glassbottle container 580 having a rubber septum cap 582 is placed into areceiving holder 586 having a rubber septum seal 588. The receivingholder 586 holds the rubber septum 582 in a fluidly sealed manner and isdisposed adjacent to the rubber septum seal 588 so as to leave a space590. Hydrogen peroxide solution from about 2% to about 50% concentrationis then introduced into the space 590 through inlet 592 to sterilize thespace 590. When the sterilization is completed the hydrogen peroxidesolution may discharge through outlet 594. Subsequent to thesterilization the dual lumen needle 596 or optionally two needles ismoved upward puncturing the rubber septum seal 588 and the rubber septum582 so as to sterilely connect the glass bottle container 580 to thesystem.

Sterile decoupling may be performed by retracting the dual lumen needle596 below the rubber septum seal 588. The rubber septum 582 can then bedecoupled from receiving holder 586 without contaminating dual lumenneedle 596.

To further maintain sterile conditions, fluid is drained out of thesystem through an isolation, one-way valve 56 so as to prevent theintroduction of virus, bacteria and pyrogen from the drain 58.

The above combination of procedures for maintaining sterile conditionslessens or greatly reduces the likelihood of pyrogens and bacteria andviruses entering the flow paths and thereby the peritoneal cavity ofpatient 50. As a result of the system being able to maintainhighly-sterile conditions, a final 0.22 μm sterilizing filterimmediately upstream of the catheter is not required before thedialysate is delivered to the patient.

The PDS system 10 of the present invention allows not only daytime oracute use but also for nighttime peritoneal dialysis treatment ofpatients. In this manner, patients can avoid the difficulties anddiscomfort that occurs with other peritoneal dialysis treatmentsrequiring hospital or clinic visits. It is advantageous to utilizenighttime treatment in order to permit the patient to lead a more normallife during the waking hours. In addition, the method of treatmentpreferably to be employed with the PDS system of the present inventionwill require less dialysate to be stored within the peritoneal cavityduring the dry period since there will be sufficient dialyzation by thecontinuous surge and flushing of the dialysate through and from theperitoneal cavity during the wet period.

In addition, the PDS system 10 is a gentler treatment system than thatwhich is obtained with the more dramatic hemodialysis. In addition, thepsychological factors inherent in hemodialysis treatment are avoided bythe present system. Furthermore, the PDS system 10 is a simpler and lesscomplicated system than is required with hemodialysis. The PDS system 10thus allows a patient to avoid the dramatic environment facing such apatient in a hospital or clinic for either hemodialysis or conventionalperitoneal dialysis treatments.

Also, by allowing the peritoneal membrane to be dry for a good portionof the day, problems otherwise present with other treatments can beavoided or minimized. Furthermore, the PDS system 10 by means of thecompact and low cost RO device or cartridge which need only be replacedonce every one to six, preferably three days, will help to reduce thecost of treatment within the range of a greater number of patients.Furthermore, the PDS system 10 will allow for shipment of small volumeprepackaged drug concentrates in a paste, liquid or dry state which canthen be combined with the ultrapure water prepared directly at thepatient's home site by means of the RO device cartridge.

In an alternative embodiment of the PDS system 10, the operation will becomputer controlled and will only require an on-off button so thatentire treatment programs can be implemented from a computer system.Furthermore, diagnostic sensors may be included in order to measure theurea and other metabolites so as to provide for a constant monitoringand desired treatment of the patient. Such a computer system will alsopermit the patient or care giver to modify the treatment stages and thevolume of treatment fluid as desired. Also, such a computer system willallow the treatment process to be fine tuned to the specific medicalneeds of the patient. In general, the PDS system 10 provides a customcare treatment as well as an improved quality of life for the patient.

One specific manner in which the PDS system 10 may control peritonealdialysis is to control the fluid flow rates through pumps 46 and 52.Typically, the total volume introduced into the peritoneum is less thatthe total volume drained out of the peritoneum. This volume differenceis due to the ultrafiltrate or excess water generated in the body whichis drawn into the peritoneum by osmotic pressure and which contributesto the total volume of water draining out. The PDS system 10 may thusset the flow through pump 52 at a greater rate than through pump 46 tocompensate for this volume difference.

Another manner of controlling the peritoneal dialysis is to set themaximum fluid pressure in the inlet line near point A to 48 inches ofwater and to set the outlet line near point B to a maximum of minus 38inches of water. This effectively prevents the pressure within theperitoneum from exceeding 30 inches of water. Preferably, the pressurewithin the peritoneum should be less than eight inches of water and mostpreferably less than 5.5 inches of water. These pressure maximums arechosen so as to minimize the adverse effect of fluid pressure within theperitoneum to cardiac output and vital capacity as disclosed in"Reduction of Vital Capacity Due to Increased Intra-Abdominal PressureDuring Peritoneal Dialysis", by L. Gotloib, et al., P. D. Bulletin, Vol.1, 63-64 (1981), which is incorporated herein by reference.

As shown in FIGS. 4 and 5, the reverse osmosis (RO) cartridge of thepresent invention has a cylindrical hollow housing 102 forming a chamber104 within which a hollow mandrel core 106 open at both ends is disposedwithin the chamber 104 so that the axis of the core 106 is coaxial tothe axis of the chamber 104. The core preferably is formed of ABSplastic and can be molded but preferably extruded. The housing is formedof pressure-containing material--steel, fiberglas, Kevlar™ or aluminumto provide a light yet strong structure.

As shown in FIG. 14, an RO multilayer assembly 108 includes a porouspermeate mesh or carrier layer 110, a first RO membrane layer 112, afeed water mesh or carrier layer 114 and second RO membrane layer 116.The RO membranes 112 and 116 are each formed of a composite, non-porous,semipermeable membrane 200, an ultrafiltration membrane 202 and apolyamide cloth 204 as shown in FIG. 15. RO membranes of this specificstructure can be obtained from FilmTec Corporation, a division of DowChemicals, with a membrane designation of BW30. Such an RO membrane isalso disclosed in U.S. Pat. No. 4,277,344 of J. E. Cadotte, assigned toFilmTec Corporation and issued Jul. 7, 1981 which is incorporated hereinby reference. The RO multilayer assembly 108 is fixed to and rolledabout the surface of the core 106 as shown in FIG. 7. An impermeableglue seal 118 is provided at about the middle of the RO multilayerassembly 108 prior to rolling and is disposed approximatelyperpendicular to the core 106 so that the glue seal 118 separates the ROmultilayer assembly 108 into two stages 120 and 122 when the ROmultilayer assembly 108 is spirally wound about the core 106. The sideedges of the RO multilayer assembly 108 are also sealed by glue bonds124 and 126. Thus the first and second stage 120, 122 are fluidlyseparated from one another. Preferably, the glue seal is made of atransparent glue capable of water vapor curing available under a tradename of H. B. Fuller Product #UR-0330. In order to provide visibility,the glue can be mixed with a coloring agent. Coloring agents includecarbon black, fiber glass, mica, metallic particles, calcium carbonateand titanium dioxide at 0.25-3% by weight of glue preferably less than1%. Particle size for the coloring agent range from 0.1 to 5 μm,preferably 1-2 μm. If carbon black is used, the glue becomes gray incolor and also results in an improved wettability and better bonding.

The housing 102 has a base 128 which is dimpled inwardly toward theinterior of chamber 104 as shown in FIG 4. The housing 102 is open atits other end which is sealed by a cap assembly 130 that is formed oftwo pieces. An integral cap member 132 made of the same plastic materialfrom which the core 106 is fabricated and an annular steel cap plate 136which at its inner end seals about a periphery of cap member 132 and atits outer end seals in a formed manner with rolled edge 138 of thehousing 102. As shown in FIG. 12, the annular steel cap plate 136provides openings 140a, 142a and 144a for an inlet tube 140 of cap 132which is coupled by suitable tubing (not shown) to the high pressurewater from pump 20 as shown in FIG. 1; the drain outlet tube 142 andoptionally 147; and a permeate or purified water outlet 144 as shown inFIGS. 9, 12A and 5. The radial ribs of the annular steel cap plates 136are optional and are not required. The core 106 contains a hollow space146 to receive therein activated carbon 145 which is held in placebetween depth filters 148 adjacent the base 128 and 150 which isadjacent the cap 132.

As shown in FIGS. 7 and 14, a first RO multilayer subassembly 21 at oneend 212 can be affixed in a longitudinal slot 214 from which themultilayer subassembly 210 is spirally wrapped around the core 106. Thisfirst multilayer subassembly comprises a porous permeate carrier layer110 and a first RO membrane layer 112. A second RO multilayersubassembly 216 can be affixed in a second longitudinal slot 218 and isalso spirally wrapped around in the same direction as the aforementionedRO multilayer subassembly 210. This second RO multilayer assembly 216comprises a feed water mesh layer 114 and a second RO membrane layer116. At the other end of the membrane multilayer subassembly 210, theedge is kept open to allow tap water under pressure to enter. The dottedcircle 220 indicates the actual radius of the complete RO multilayerassembly when wound onto the core 106.

The RO device, as shown in FIG. 4, also includes a pressurized container166 which is generally cylindrical having a closed end 168 restingadjacent the dimpled end of base 128 and secured by a hot melt glue bead169. The other end of pressurized container 166 is open and isdimensioned so as to receive the rolled RO second stage 122 therein. Thecore 106 is sonically welded to the inner base wall of the pressurizedcontainer 166. An O-ring 170 provides additional sealing to facilitatethe potting of glue seal 119 which is adjacent the glue seal 118 and theinner wall of pressurized container 166. If desired, additional O-ringscan be provided as well as other sealing means according to methodsknown to those of the sealing art. For example, an adhesive seal can beprovided next to the O-ring above the glue seal 118 and below the O-ringafter assembly within the pressurized container 166. In this manner, thesecond stage 122 is fluidly sealed from the first stage 120. The depthfilter 148 is pressed in contacting relationship with a bead 172 whichhelps to seat the core 106 within the pressurized container 166.However, the passageways 125 are kept spaced from the base ofpressurized container 166, as shown in FIG. 4 and 12B so that the fluidcommunication of those passageways is maintained with a chamber 174formed therein.

As shown in FIG. 7, the core 106 has additional passageways 222 whichare simply provided to lighten the weight of the core 106 and do notprovide any operational function in the RO device.

In a preferred configuration, a small RO device may have an effective ROmembrane surface for each of the stages 120 and 122 of about 0.5 squarefeet to about 1.5 square feet. A large RO device may requiresubstantially more surface area ranging up to industrial sizes ofhundreds of square feet. The rejection rate of the first stage is atleast 90%. The rejection rate of the second stage is at least 60%. Theoverall performance of both stages in combination will be at least 96%rejection. The operating pressures across the membranes of the first andsecond stages are preferably about 125 psi each. The dimension of thehousing 102 of the RO device is preferably about 7 inches in length, 2.3inches in diameter. The dimension of the hollow core 106 of the ROdevice is preferably about 6.3 inches in length and about 1.25 inches indiameter.

In operation, the various fluid paths of the RO device are illustratedin FIG. 6, which shows that pressurized tap water enters through inlet140 and thereafter through passageway 152. Upon entering the first stage120, the pressurized water passes through the RO multilayer assembly.The first portion of purified water from the tap water is passed intothe longitudinal passageway 123 and toward the cap member 132 andthereafter is directed by guide 124 through depth filter 150 (See FIG.4) into the hollow space 146 containing activated carbon 145. Uponpassing through the length of the hollow space 146, the now chemicallypurified water passes through depth filter 148 (See FIG. 4) and thenthrough guide 125 to the chamber 104 from which the chemically purifiedwater enters in the RO multilayer assembly of the second stage 122. Uponfurther filtration within second stage 122, the finally purified waterpasses into passageway 154 and exits through permeate outlet 144. Thedrain water from the first stage 120 enters into passageway 156 and thenthrough restrictor 224 as indicated in FIG. 7 and described below inFIGS. 28-31. The second stage 122 enters into a passageway 158 and thenthrough restrictor 226 as indicated in FIG. 7 and described below inFIG. 28-31. The fluid from restrictors 224 and 226 combine within guide143 and subsequently drains through outlet 142. Alternatively, the fluidfrom the first stage restrictor 224 can drain directly through optionaloutlet 147 and the fluid from the second stage restrictor 226 can draindirectly through outlet 142 as shown in FIG. 6.

An alternative embodiment of the RO device according to the presentinvention is illustrated in FIGS. 8-11, wherein structural featurescommon to the embodiment shown in FIG. 4 are depicted by the likenumber. The main difference in construction from that shown in FIG. 4 isthat the first stage 122 is away from the inlet 140 and is fittedagainst the inner wall of the pressurized container 166 and the secondstage 120 is closest to the inlet 140.

In operation, the various fluid paths of the RO device are illustratedin FIG. 10, which shows that pressurized tap water enters through inlet140 and thereafter through passageway 123 within core 106. Uponapproaching the base 128 of pressurized container 106 the pressurizedwater enters through guide 125 into passage chamber 174 and thereafterinto the RO multilayer assembly of the first stage 122. The firstportion of purified water from the tap water is passed into thelongitudinal passageway 146 and back toward the base 128 which thereuponadmits through guide 126 the first purified portion into the hollowspace 146 containing activated carbon 145 within the hollow core 106.Upon passing through the length of the hollow core 106, the nowchemically purified water enters the chamber 104 through guide 127 fromwhich the chemically purified water enters into the RO multilayerassembly of the second stage 120. Upon further filtration within secondstage 120, the finally purified water passes into passageway 156 andexits through outlet 144. The drain water from the first stage 122enters passageway 158 and then through a restrictor as described belowin FIG. 28-31. The drain water from the second stage 120 enterspassageway 154 and then through another restrictor. The fluid from bothrestrictors combine within guide 143 and subsequently drains throughoutlet 142. Alternatively, the fluid from the first stage restrictor candrain directly through another outlet (not shown) and the fluid from thesecond stage restrictor can drain directly through outlet 143.

In both of the above embodiments shown in FIGS. 4 and 8, the ROmultilayer assembly which is wound about the hollow core 106 is attachedonto the core 106 by means of two slots 214 and 218 as shown in FIGS. 7and 13. Preferably, one or more of the ends of the RO multilayerassembly is attached to the hollow core 106 by means of an adhesivestrip 228 without placing the end into any slot as shown in FIG. 11. TheRO multilayer assembly is thereby divided into two parts in itsattachment to the core 106. FIG. 14 schematically illustrates thevarious layers of the RO multilayer assembly. As shown in FIG. 13, thefirst part which is attached to slot 218 comprises a porous mesh layer114 and a second RO membrane layer 116. The second part which isattached to slot 214 comprises a porous permeate layer 110 and a firstRO membrane layer 112. In operation, the unpermeated tap water isdrained out from the porous mesh layer 114 and through passageways 158and 156 within core 106 to drain outlet 142. The purified water whichhas permeated through the RO membrane layer 112 and 116 passes from theporous permeate layer 110 through passageways 123 and 154 within thecore 106 and to permeate outlet 144.

When the multilayer is wound about the core, the RO multilayer assemblyis configured as shown in FIG. 14. The first and second RO membranelayers 112 and 116 are faced in opposite directions from each otherbecause of the structure of the RO membrane layer which is shown in FIG.15. Adhesive beads 206 are disposed against the porous mesh layer 114and the porous permeate layer 110 as shown to form the RO multilayerassembly. The RO membrane layers 112 and 116 comprise a nonporous,semipermeable membrane 200 an ultrafiltration membrane 202 and apolyamide cloth 204 as shown in FIG. 15. The RO membrane layers 112 and116 in FIG. 14 illustrate the relative position of the nonporous,semipermeable membrane 200 with respective to the other layers.Specifically, the nonporous, semipermeable membrane layers of the ROmembrane layers 112 and 116 are adjacent to the porous mesh layer 114.

Another alternative embodiment of the RO device according to the presentinvention is illustrated in FIG. 16, wherein structural features commonto the embodiment shown in FIG. 4 are depicted by like number. As shownin FIG. 16, the RO device 400 has a central core 106 which is positionedwithin an end base cap 402 and secured to adjacent base 128 of housing102 by hot melt glue bead 169. As shown in FIG. 17, four RO multilayersubassemblies 316, 318, 320 and 322, are affixed in longitudinal slots324, 326, 328 and 330, respectively, in core 106. Alternatively, theends of the subassemblies may be attached to the core by adhesive beads.RO multilayer subassembly 316 is formed of a nonporous, semipermeablemembrane layer 302 and a porous permeate layer 304. The RO multilayersubassembly 318 is similarly formed of a nonporous semipermeablemembrane layer 306 and a porous permeate layer 308. Likewise, the ROmultilayer subassembly 320 is similarly formed of a nonporoussemipermeable membrane layer 310 and a porous permeate layer 312. The ROmultilayer subassembly 322 is formed of a nonporous semipermeablemembrane layer 314 and a porous mesh layer 300. Unpermeated tap waterexits through passageway 158 and drain outlet 142 and sterilized waterexits through passageway 123 and permeate outlet 144. As shown in FIG.18 which is taken in the opposite direction of FIG. 17, the RO membranes302, 306, 310 and 314 are spirally wound around the core 106 as well aseach other. Alternatively, FIG. 18 represents an RO configuration inwhich the RO membranes, if desired, can be rolled about core 106 in theopposite direction to that shown in FIG. 17. Interleafed between the ROmembranes are the porous mesh layer 300 and the porous permeate layers304, 308 and 312. When the static pressure within the porous mesh layer300 is TP, the static pressure within the porous permeate layers 304 and312 is 1/2 TP and the static pressure within the porous permeate layer308 is about 0.05 TP. The various flow paths are shown in FIG. 18 aswell. In operation, the alternative embodiment of the RO device of FIG.16-19 is substantially the same as that described with reference to theRO device illustrated in FIGS. 4 and 8. However, the alternative ROdevice of FIG. 18 passes the water from the high pressurized sourcethrough the two RO stages which are formed of the four RO multilayersubassembly of FIG. 17 before passing through the activated carbon 145contained in the hollow space 146 within core 106 between depth filters148 and 150. An exploded cross-sectional view of the RO multilayerassembly of FIG. 18 is shown in FIG. 19. Adhesive beads 206 are disposedagainst the layers as shown to form the RO multilayer assembly.

The activated carbon serves to remove chloramine as well as dissolvedgases from the tap water. In the event that the water supplied to the ROdevice is already free of chloramines, then there is no need tochemically treat the water. In addition, chemical treatments can beutilized for removal of other chemical species as well. Both thesemi-permeable membranes in the RO device of FIG. 4 and the alternativeembodiments of FIGS. 8 and 16 are preferably formed of polyamide.However, other semi-permeable membrane layers can be utilized as well.

In both embodiments of the RO device as illustrated and describedherein, the RO membranes are formed in a spiral configuration so as tomaximize the velocity of tap water across the membrane and to minimizethe concentration polarization at the membrane surfaces within as smalland compact a housing as possible. This avoids the need to provide forextensive lengths of housing to enclose RO membranes as found in typicalapplications.

Yet another alternative embodiment of the RO device according to thepresent invention is illustrated in FIG. 20. The RO device 702 includesa generally cylindrical housing 704 having an end cap 706 in which isdisposed centrally an inlet port 708 that is fluidly coupled to thesource of water to be purified. The other end has a seal cap 710 that isscrewed on by threads which engage cooperating threads 712 on theadjacent end portion of housing 704. The seal cap 710 has a waste outlet714 and a permeate outlet 716. Positioned internally within the housing704 is a core 701 that is generally cylindrical and is formed of threelongitudinal passageways as shown in FIG. 20A. Two of the passageways720 and 722 are of like shape and together form half of the core 701.The remaining passageway 724 includes activated charcoal for the samepurposes as discussed above in connection with the prior embodiments.Passageway 720 is coupled through outlet 714 for passage of waste water.The other like passageway 722 provides for passage of permeate and iscoupled to the outlet 716 in seal cap 710. A first RO stage 726 ispositioned within chamber 728 formed within housing 704. The secondstage 729 is positioned within housing 704 in chamber 730 adjacent sealcap 710. The first and second stages are connected through a restrictor705. The restrictor 705 is designed to adjust the backpressure withinthe first and second stages 726 and 729 so as to provide the desiredwater flow rate across the membranes. The first and second RO stage's726 and 729 are separated by a core support carrier 732 which is snuglyfit within housing 704. The support carrier 732 has a U-shaped channel734 that extends along the periphery of carrier 732 to receive an O-ring736 as shown in FIG. 20. In operation, water enters through port 708 andinto chamber 728 wherein it enters into the first RO stage 726. Afterfiltration, the filtered portion of the water passes through radialopenings 741 in core 701 into passageway 724. Upon passing through theactivated charcoal 718 within passageway 724, the partially filteredwater passes through radial opening 740 in core 701 into chamber 730 andfrom there into the second RO stage as shown in FIG. 20. Upon furtherfiltration, the permeate passes out through outlet 716. The waste waterfrom the first stage passes through radial openings 742 into the returnpassageway 720 and from the second stage through radial opening 744 alsointo the waste passageway 720 and finally out the waste outlet 714.

In yet another alternative embodiment of the RO device according to thepresent invention as shown in FIG. 21, the RO device 802 includes acylindrical housing 804 that includes a first RO stage 806 and a secondRO stage 808 which are wrapped around a central core 810. The centralcore 810 has an inlet port 812 through which water passes into aninterior chamber 814 and thereafter through openings 816 into thechamber 818 in which the first stage 806 is positioned. Upon passingthrough the first stage 806, the filtered water passes through radialopening 820 in core 810 and thereafter through radial opening 822 into acentral portion containing activated charcoal 823. Upon passing throughthe charcoal 823, the purified water passes out through radial opening824 into chamber 826 and through radial opening 828 in core 810 throughantechamber 830 and therefrom through opening 832 into chamber 834 inwhich the second RO stage 808 is positioned. Upon passage through thesecond RO stage, the permeate exits through radial opening 836 and outthrough port 838. The waste water from the first RO stage exits throughdrain port 840 while the waste water from the second RO stage 808 passesthrough the drain port 842.

In order to provide for proper water flow across the RO multilayerassembly 108, the cylindrical passageway tubes in core 810 are designedin accordance with the Bernoulli equation so that their diameter andlength are calculated to produce a static pressure drop across both ROmultilayer assemblies 108 of the first stage 806 and second stage 808.The pressure drop produces the desired water flow rate across themembranes. For example, the flow across the second membrane is less thanacross the first. Static pressure across the first membrane is twicethat across the second. This yields a different geometry for the secondrestrictor. Balancing the spiral resistance with the cylindricalresistance is the key to the proper functioning of the RO Device.

FIGS. 28 and 29 illustrate a linear restrictor having a barrel 522 and aneedle 520 of proper internal diameter and path length to produce therequired static pressure drop across both RO multilayer assemblies.FIGS. 30 and 31 illustrate a helical restrictor which serves the samefunction. The advantage of the helical restrictor 524 is that thepathlength along the restrictor 524 within sleeve 526 can be manuallyadjusted by screwing the restrictor 524 further into or out of thesleeve 526 by way of a slot 528. The dimension of the helical restrictor524 is preferably about 1 inch in length, 0.150 inch in diameter withabout 16 threads per inch and a thread width of 0.020 inch. Theeffective path length of such a helical restrictor 524 is thereforeabout 5.938 inches. The restrictors are disposed within the passagewayswhich fluidly connects the drains of RO multilayer assemblies of thefirst and second stage. Alternatively, the restrictor may be placed atthe outlet drain of stage one and the outlet drain port of the device.

In the operation of the present peritoneal dialysis system (PDS) 10 ofthe present invention, the potable water can be heated to about 40° C.before passing through the RO device 22 as shown in FIG. 1. The highertemperature increases the efficiency of the reverse osmosis process.Specifically about 600 ml/min of potable water can be heated from about20° C. to about 70° C., preferably up to 40° C. In order to decrease theheating demand on heater 18, the heat exchanger 16 transfers heat fromthe waste water from RO device 22 and patient 50 to the potable waterbefore the potable water passes through heater 18.

The configuration of the heat exchanger 16 is similar to that of the ROdevice 22 but only requires thin non-permeable membrane multilayerassemblies with porous spacers spirally wound about a hollow core 602 asshown in FIG. 22. Specifically, the heat exchanger 16 contains a firstmultilayer assembly 604 as shown in FIG. 23 which includes a firstporous spacing layer 606 and a non-permeable membrane layer 608.Adhesive beads 610, 612 and 614, preferably of RTV silicon, are appliedalong the side edges as shown in FIG. 24. A partial adhesive bead 616 isapplied to the free end along a portion thereof. A second multilayerassembly 618 shown in FIG. 25 includes a second porous spacing layer 620and a non-permeable membrane layer 622 that are disposed on the firstmultilayer assembly 604 such that the first and second porous spacinglayers 606 and 620 are interleafed between the two non-permeablemembrane layers 608 and 622. Adhesive beads 624, 626 and 628, alsopreferably of RTV silicon, are applied along the side edges ofmultilayer assembly 618 as shown in FIG. 26. A partial adhesive bead630, oppositely disposed to partial adhesive bead 616 in FIG. 24, isapplied to the remaining free end of multilayer assembly 618 along aportion thereof.

As shown in FIG. 22, the first and second multilayer assemblies 604 and618 are wrapped about core 602, preferably made of ABS plastic, and areimbedded within the pressurized container 632 which is similar tocontainer 166 in the RO device of FIG. 4. The end cap 634 seals the heatexchanger unit 16 within a housing (not shown). An O-ring 636 helps toseal the unit 16 within the pressurized container 632. The RTV siliconsealant is shown generally in the assembled form in FIG. 22 at 638. Thehot waste water enters through part 640 and cold discharge water exitsthrough port 642 after passing through longitudinal passageway 644.Radial holes 646 in the core 602 admit the spent or cold waste waterfrom between the membrane multilayer assemblies into the passageway 644.Cold potable water enters through port 647. Hot potable water which hasreceived heat transferred from the hot waste water between the membranemultilayer assemblies passes through port 648 in cap 634 after exitingthrough radial holes 650 in core 602.

In operation, hot waste water passes through the first porous spacinglayer while tap water passes through the second porous spacing layer.The transfer of heat from the hot waste water to the potable wateroccurs across the non-permeable membrane layers as the waste and thepotable water flow spirally in a countercurrent or concurrent flow path.The porous spacing layer is preferably polypropylene mesh. Thenon-permeable membrane layer is preferably a polyester film such asMelinex® or a foil, preferably metallic.

Heat transfer efficiency of the heat exchanger 16 is dependent on themembrane material used, the water flow path width, the path length aswell as the amount of area available for heat transfer. Consideration ofheat transfer efficiency, however, must be balanced with the unfavorablepressure drop through the heat exchanger 16. A preferred configurationhas a heat transfer area of about 300 sq. inches and a pressure drop ofabout 4 psi at 600 ml/min flow rate.

A more general illustration of the use of the RO device is presented inFIG. 27 which illustrates a source of fluid or water 500 which is passedon to a RO device 502. Here again, the waste fluid is passed on to adrain 504 while the purified fluid is passed on to a concentration, mix,store and/or control system 506. Storage can be provided in suitablebags which thereafter can be utilized when desired for the patient 508or other end uses 510. If denied, a portion of the purified fluid afteruse can be returned to the source along fluid path 512. Similarly, someor all of the waste from the RO device 502 can also be returned to thesource and thereafter passed on for purification within the RO device502.

According to the preferred design, the RO cartridge may be used forthree to six days during a weekly treatment and thereafter is discarded.Discarding the cartridge is necessary because of carbon contaminationbuild-up and to avoid a sterility breach. For this reason, there is noneed to sterilize while in use the RO membranes so as to remove anycontaminants whether chemical or particulate as is required with presentsystems. In order to provide an RO cartridge suitable for home use, theRO cartridge is designed for optimization of compactness and space aswell as performance so as to minimize the cost. This will enable thepatient to obtain home treatment without the need to stock a largequantity of sterile water and also further avoids the need to providefor multiple hook-ups as is required in the case of CAPD treatment.Discussion of the concerns and problems relating to connection tomultiple water bags is presented in an Optum® brochure entitled "TheHands-Free Exchange For Your CAPD Patients" and U.S. Pat. No. 4,840,621which are incorporated herein by reference.

By means of the use of a dual RO stage system, less expensive ROmembrane multilayer assemblies can be utilized so as to still obtainpreferably at least a 96% rejection rate. Moreover, the dual ROmultilayer assemblies provide a redundancy which is medically desired inthe event that one membrane fails. The drastic medical consequences ofintroducing pyrogen, virus or bacteria in the peritoneal cavity are thusavoided by the present RO device.

The RO device and system of the present invention accordingly overcomethe problems of known filtration devices for use in peritoneal dialysisand provide sterile water solutions suitable for peritoneal dialysis andother uses as well and which can easily maintain the desired sterileconditions. Because of the modular design of the present system, thereverse osmosis device and other system components which are in contactwith the water can be periodically disposed of and replaced by newsterile components. The need to have a complicated method ofsterilization implemented by the user is therefore avoided.

FIG. 32 illustrates one efficient manner of producing the RO device ofthe present invention. Specifically, electromagnetically activatableadhesive beads are applied onto the porous mesh layer and the porouspermeate carrier layer along the edge and the middle of the multilayerassembly as shown. The manner in which the adhesive bead is applied canbe by a roller coating method in which the adhesive is heated in a potand picked up by a transfer roller (not shown). The transfer roller thenprints the adhesive strips 206 onto the porous mesh layer or the porouspermeate carrier layer (see FIGS. 14 and 19) in a continuous manner asthe layers move across the transfer roller. The layers are then combinedand rolled onto a hollow core 106. Simultaneous to the rolling of thelayers to form the multilayer assembly, the adhesive strips 206 areheated by the induction coils 528. The softened adhesive strips 206 thenbond the RO multilayer assembly together as the adhesive cools withinthe wound layers.

A representative example of such an electromagnetically activatableadhesive may be obtained from Emabond Systems of Ashland ChemicalCompany, a division of Ashland Oil, Inc. and is taught in U.S. Pat. No.3,620,875, issued Nov. 16, 1971 which is incorporated herein byreference.

FIG. 33 illustrates another manner of producing the RO device of thepresent invention. The adhesive bead 200 has already been applied to themesh and permeate layers of the RO multilayer assembly. The assembly 108is subsequently wound about the hollow core 106 and then inserted into aflexible silicone bladder 530 and attached to cap 532 by ring 534. Thewound assembly is then evacuated by vacuum 536 to thereby ensure closecontact between the layers of the assembly and the core 106. Inductionheating is then applied by coils 538 while the assembly is in theevacuated state so as to bond the layers together. The vacuum in bladder530 is released by filtered air from 540 after cooling of the adhesivebead has occurred.

FIG. 34 illustrates a method of attaching the integral cap member 132 ofthe RO device to the hollow core 106 by sonic welding. The ultrasonicvibration of the sonic horn 550 is transmitted through energytransmission guides 552 to energy directors 554 so as to focus thevibration energy to the point of contact with the hollow core 106.Additionally, another sonic horn 556 is used to sonically weld the innerbase wall of the pressurized container 166 to the other end of thehollow core 106 through similar energy transmission guides 558 andenergy directors 560. Alternatively, the energy directors may be placedon the hollow core 106. Such directional welding can be accomplished at20 and 40 kHz frequencies. FIGS. 12A and 12B illustrate the energydirectors 554 and 560 respectively in a ridge design so as to seal thepassageways of the hollow core to the integral cap member 32 and innerbase wall of the pressurized container 166 as shown in FIG. 4. Thepattern shown in FIG. 12A and B allows for the sealing of thepassageways of the core to the guides of the cap so as to provide fluidpassageway inner connections.

The ridge design of the integral cap member 132 shown in FIG. 12A isadapted to provide the RO device of FIG. 6 with the guide 124 connectingpassageway 123 and hollow space 146; guide 143 connecting passageways156 and 158 to waste drain outlet 142; the connection between inlet hole140 and passageway 152; and the connection between permeate outlet hole144 and passageway 154.

The ridge design of the inner base wall of the pressurized container 166shown in FIG. 12B is adapted to the RO device of FIG. 6 so as to sealthe ends of the passageways of the core 106. Guide 125 connects thehollow space 146 of the core 106 to the chamber 104 which allows thechemically purified water to enter from the hollow space 146 to the ROmultilayer assembly of the second stage 122.

The present invention has been described in detail with particularemphasis on the preferred embodiments thereof. However, it should beunderstood that variations and modifications may occur to those skilledin the art to which the invention pertains.

We claim:
 1. Method for purifying fluid from a source comprising:a.passing fluid in a spiral fluid manner from the source through a firstspiral wound reverse osmosis means being in fluid communication with thesource so as to purify at least a portion of the fluid from the source;and b. passing the purified first portion of fluid in a spiral flowmanner through a second spiral wound osmosis means being in fluidcommunication with said first reverse osmosis means to receive at leastsome of the purified portion of fluid for further purification of atleast a further portion of the fluid.
 2. Method for purifying water froma source comprising:a. passing water in a spiral fluid flow manner fromthe source through a first spiral wound reverse osmosis means being influid communication with the source so as to purify at least a firstportion of the water from the source; and b. passing the purified firstportion of water in a spiral fluid flow manner through a second spiralwound reverse osmosis means being in fluid communication with said firstreverse osmosis means to receive the purified first portion of fluid forfurther purification of at least a second portion of the water. 3.Method for purifying water from a source comprising:a. passing water ina spiral fluid flow manner from the source through a first spiral woundreverse osmosis means being in fluid communication with the source so asto purify at least a first portion of the water from the source; b.passing the purified first portion of water through chemical means beingin fluid communication with said first reverse osmosis means to receivesaid first purified portion of water and for removal of at leastchemical contaminants from said first purified portions of water; and c.passing the chemically purified water in a spiral fluid flow mannerthrough a second spiral wound reverse osmosis means being in fluidcommunication with said chemical means to receive the chemicallypurified water for purification of at least a second portion of thechemically purified water, said second reverse osmosis means also beingin fluid communication with a first outlet and a second outlet so as topermit passage of said second portion of purified water through saidfirst outlet and for passage of wastewater through said second outlet.4. Method for purifying water from a source comprising:a. passing waterin a spiral fluid flow manner from the source through a first spiralwound reverse osmosis means being in fluid communication with the sourceso as to purify at least a first portion of the water from the source;b. passing the purified first portion of water in a spiral fluid flowmanner through a second spiral wound reverse osmosis means being influid communication with said first osmosis means to receive thepurified first portion of water for further purification of at least asecond portion of the water; and c. passing the purified second portionof water through chemical means being in fluid communication with saidsecond reverse osmosis means to receive said second purified portion ofwater and for removal of at least chemical contaminants from saidpurified second portion of water, said chemical means also being influid communication with an outlet so as to permit passage of saidchemically purified water through said outlet.
 5. The method accordingto claim 4 further comprising passing the chemically purified waterthrough a filtration means for further purification.